Nanoparticle (NP)/cell interactions, particularly in complex in vivo microenvironments, are regulated by an intricate spatiotemporal interplay of numerous biological and NP characteristics. Multiple NP physicochemical properties including, at the most basic level, material composition, size, shape, surface charge, and surface chemistry, have all been reported to play significant roles.1-3 However, the relative importance of these diverse NP physicochemical properties in regulating interactions with various biological systems remains incompletely understood.1 As such, achieving or avoiding cell-type specific interactions in vivo requires an improved understanding of the relative roles of these diverse NP properties, as well an ability to exert a high level of control over these properties during NP synthesis.
While the existing paradigm dictates that decreased size, neutral or negative zeta (ζ) potential, and extent of PEGylation are correlated with increased circulation time (i.e., reduced interaction with host cells),4 the manner in which these combined physicochemical properties conspire to direct in vivo cellular interactions has not been elucidated through careful systematic studies, and the nature of these interactions is likely to vary significantly by particle formulation and cell type.
An ability to simultaneously load NP's with a variety of diagnostic and/or therapeutic agents and to more effectively exploit NP shape and pore size would facilitate the identification and treatment of a numerous disorders, including cancers and bacterial and viral infections.